bones

Define Bone ?

Bones are rigid organs that form part of the endoskeleton of vertebrates. They function to move, support, and protect the various organs of the body, produce red and white blood cells and store minerals

Define Bone ?

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OssificationOssification is the process by which bone is formed from cartilage. The cartilage cells die off and are calcified to produce bone.

As a baby grows the cartilage becomes bone and hardens. This is part of the process of bone growth.

In the womb the skeleton of the foetus is initially formed from an elastic tissue called cartilage (except for the clavicle and parts of the cranium).

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Types of Ossification

Intramembranous Ossification

&

Endochondral Ossification

Intramembranous Ossification

• Some bones of the skull (frontal, parietal, temporal, and occipital bones), the facial bones, the clavicles, the pelvis, the scapulae, and part of the mandible are formed by intramembranous ossification

• Prior to ossification, these structures exist as fibrous membranes made of embryonic connective tissue known as mesenchyme.

• Some bones of the skull (frontal, parietal, temporal, and occipital bones), the facial bones, the clavicles, the pelvis, the scapulae, and part of the mandible are formed by intramembranous ossification

• Prior to ossification, these structures exist as fibrous membranes made of embryonic connective tissue known as mesenchyme.

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Formation of the Bony Skeleton• Mesenchymal cells first

cluster together and start to secrete the organic components of bone matrix which then becomes mineralized through the crystallization of calcium salts. As calcification occurs, the mesenchymal cells differentiate into osteoblasts.

• The location in the tissue where ossification begins is known as an ossification center.

• Some osteoblasts are trapped w/i bony pockets. These cells differentiate into osteocytes.

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• The developing bone grows outward from the ossification center in small struts called spicules.

• Mesenchymal cell divisions provide additional osteoblasts.• The osteoblasts require a reliable source of oxygen and

nutrients. Blood vessels trapped among the spicules meet these demands and additional vessels branch into the area. These vessels will eventually become entrapped within the growing bone.

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• Initially, the intramembranous bone consists only of spongy bone. Subsequent remodeling around trapped blood vessels can produce osteons typical of compact bone.

• As the rate of growth slows, the connective tissue around the bone becomes organized into the fibrous layer of the periosteum. Osteoblasts close to the bone surface become the inner cellular layer of the periosteum.

• Initially, the intramembranous bone consists only of spongy bone. Subsequent remodeling around trapped blood vessels can produce osteons typical of compact bone.

• As the rate of growth slows, the connective tissue around the bone becomes organized into the fibrous layer of the periosteum. Osteoblasts close to the bone surface become the inner cellular layer of the periosteum.

Endochondral Ossification

• Begins with the formation of a hyaline cartilage model which will later be replaced by bone.

• Most bones in the body develop via this model.• More complicated than intramembranous because the hyaline

cartilage must be broken down as ossification proceeds.• We’ll follow limb bone development as an example.

Endochondral Ossification – Step 1

• Chondrocytes near the center of the shaft of the hyaline cartilage model increase greatly in size. As these cells enlarge, their lacunae expand, and the matrix is reduced to a series of thin struts. These struts soon begin to calcify.

• The enlarged chondrocytes are now deprived of nutrients (diffusion cannot occur through calcified cartilage) and they soon die and disintegrate.


• Blood vessels grow into the perichondrium surrounding the shaft of the cartilage. The cells of the inner layer of the perichondrium in this region then differentiate into osteoblasts.

• The perichondrium is now a periosteum and the inner osteogenic layer soon produces a thin layer of bone around the shaft of the cartilage. This bony collar provides support.


• Blood supply to the periosteum, and capillaries and fibroblasts migrate into the heart of the cartilage, invading the spaces left by the disintegrating chondrocytes.

• The calcified cartilaginous matrix breaks down; the fibroblasts differentiate into osteoblasts that replace it with spongy bone.

• Bone development begins at this primary center of ossification and spreads toward both ends of the cartilaginous model.

• While the diameter is small, the entire diaphysis is filled with spongy bone.

Notice the primary ossification centers in the thigh and forearm bones of the above fetus.


• The primary ossification center enlarges proximally and distally, while osteoclasts break down the newly formed spongy bone and open up a medullary cavity in the center of the shaft.

• As the osteoblasts move towards the epiphyses, the epiphyseal cartilage is growing as well. Thus, even though the shaft is getting longer, the epiphyses have yet to be transformed into bone.


Around birth, most long bones have a bony diaphysis surrounding remnants of spongy bone, a widening medullary cavity, and 2 cartilaginous epiphyses.

At this time, capillaries and osteoblasts will migrate into the epiphyses and create secondary ossification centers. The epiphysis will be transformed into spongy bone. However, a small cartilaginous plate, known as the epiphyseal plate, will remain at the juncture between the epiphysis and the diaphysis.

Articular cartilage Epiphyseal plate

Growth in Bone Length

• Epiphyseal cartilage (close to the epiphysis) of the epiphyseal plate divides to create more cartilage, while the diaphyseal cartilage (close to the diaphysis) of the epiphyseal plate is transformed into bone. This increases the length of the shaft.

•As a result osteoblasts begin producing bone faster than the rate of epiphyseal cartilage expansion. Thus the bone grows while the epiphyseal plate gets narrower and narrower and ultimately disappears. A remnant (epiphyseal line) is visible on X-rays (do you see them in the adjacent femur, tibia, and fibula?)

At puberty, growth in bone length is increased dramatically by the combined activities of growth hormone, thyroid hormone, and the sex hormones.

Growth in Bone Thickness

• Osteoblasts beneath the periosteum secrete bone matrix on the external surface of the bone. This obviously makes the bone thicker.

• At the same time, osteoclasts on the endosteum break down bone and thus widen the medullary cavity.

• This results in an increase in shaft diameter even though the actual amount of bone in the shaft is relatively unchanged.

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Functions of the skeletonThe skeleton performs many functions in the body.

Shape – The skeleton gives us our shape and determines our size.

Blood cell production – blood cells are made in the bone marrow.

Movement – The skeleton allows us to move. Muscles are attached to the bones and move them as levers.

Protection – The skeleton protects delicate parts of the body like the brain and lungs.

Support – The skeleton supports muscles and organs.

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Bone• 206 bones in the human skeleton• Provide support, anchorage for muscles and protection for organs eg

ribs• Bone is a storage area for calcium and phosphorous salts and has an

important role in blood formation• Before birth the skeleton is made of cartilage most of which is

gradually replaced by bone via a process called ossification.• Bones of the human skeleton can be divided into long bone and flat

bones• Long bones are tubular and weight bearing and are made of a dense

outer layer of compact (cortical) bone and central region (medulla) made up of trabecular (spongy) bone

• Trabecular bone makes up most of the short, flat and irregular shaped bones and the epiphyses (ends) of the long bones

• It is much lighter than cortical bone and has a good strength to weight ratio

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1. Less calcium intake

2. Age

3. Smoking

4. Diet

5. Long use of corticosteroids

6. High body mass

What are the reason for bone loss ?

Bone loss in women occurs fastest in the first few years after menopause, but bone loss continues into old age

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Issues ?

Arthritis &

osteoporosis

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Arthritis and osteoporosis are two distinct conditions that are very common, especially in older

individuals. While osteoporosis generally affects older women who are of postmenopausal age, arthritis can affect any individual at any time. In

some cases, the conditions can be combined into a disease which is known as arthritis osteoporosis or

osteoarthritis. Arthritis osteoporosis is a disease that attacks the bone joints as well as bone mass.

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Osteoporosis

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• Osteoporosis is a chronic disease that has late clinical consequences and has been referred to as a silent epidemic because there are no associated signs or symptoms before fracture.

Risk factors for Osteoporosis• Age- bone mineral density (BMD) decreases with age• Hormones- lower levels of oestrogen after menopause

accelerate bone loss due to increased activity of osteoclasts.

• Premature menopause or hysterectomy causes earlier acceleration of bone loss. Likewise surgical or chemical castration in men

• Gender- women are at increased risk of osteoporosis as they start out with smaller bones and bone mass compared to men

• Genetic factors- family history of osteoporotic fracture, especially hip fracture, increases risk

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CALCIUM

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The Role of Calcium

Calcium is needed for our heart, muscles, and nerves to function properly and for blood to clot. Inadequate calcium significantly contributes to the development of osteoporosis. Many published studies show that low calcium intake throughout life is associated with low bone mass and high fracture rates. National nutrition surveys have shown that most people are not getting the calcium they need to grow and maintain healthy bones. To find out how much calcium you need, see the Recommended Calcium Intakes (in milligrams) chart

Calcium is needed for our heart, muscles, and nerves to function properly and for blood to clot. Inadequate calcium significantly contributes to the development of osteoporosis. Many published studies show that low calcium intake throughout life is associated with low bone mass and high fracture rates. National nutrition surveys have shown that most people are not getting the calcium they need to grow and maintain healthy bones. To find out how much calcium you need, see the Recommended Calcium Intakes (in milligrams) chart

Calcium Homeostasis

First, Let’s Take a Look at This Diagram…… Homeostasis of Calcium

Where Do I Get My Calcium?

% 70 inorganic matrix composed of Calcium Salts in Hydroxyapatite

Ca10(PO4)6(OH)2.The skeleton is resevoir for the

minerals Calcium (and phosphorous).

Resorption: the process of dissolving bone and releasing its minerals into the blood for other uses. The OSTEOCLAST secretes ACID PHOSPHATASE or sometimes HCL to digest bone matrix. Secreted by lysosomes.

Resorption and Remodeling

Resorption

Osteoclasts do this using HCL and ACID PHOSPHATASE to dissove bone matrix

Remodeling

Ostoblasts do thisCollagen fibers and

hydroxyapatite matrix

Calcium alone is not enough

• Important co-factor nutrients that work with calcium for healthy bones

Vitamin D3

MagnesiumVitamin C

Folic Acid, B12, B6SiliconBoron

Vitamin KSelenium

Zinc, Copper, ManganeseLycopene

Its Role in Calcium Homeostasis

VITAMIN DTThe vitamin That Works

Like a hormone

To Make Me D, Warm Me Up and Hydroxylate Me..3X!

Vitamin D3 Recommendation• Vitamin D3 continues to be overlooked – despite standard

medical care, research shows that over 50% of North Americans with osteoporosis have inadequate Vitamin D status!

• Supplementation studies at 800 IU (the exact dosage in the bone builder blend) show reduced fracture incidence and decreases cancer risk

• National Osteoporosis Foundation recommends 400-800 IU Vitamin D3 daily.

• Health Canada is now recommending increasing upwards to 2000 IU daily

Vitamin D3 at work

• Drives bone health, measured best by 25OH)D test

• Helps calcium be absorbed into bone-building cells

• Inhibits formation of bone breakdown cells

• Helps to prevent Calcium loss through the kidneys

• Assists in the absorption of Calcium from the intestines.

(Holick M. Mayo Clin Proc 2006)

Vitamin D Deficiency Diseases

• 16 different types of cancer• 62% increased risk of heart disease & stroke • Multiple sclerosis• Juvenile Diabetes• Influenza• Osteoporosis• Fracture Incidence• Large population studies show that dietary Vitamin D3

(or sunlight exposure) is associated with protection against osteoporosis and fractures.

(Nieves. Am J Clin Nutr 2005)

(Circulation: Jan 7, 2008)

How Does “D” Compare To Hormones?

Vitamin D3 is not secreted by a classical endocrine gland, the active form of the hormone is released from the kidney and acts at distant sites or locally.

Each of the forms of vitamin D is hydrophobic, and is

transported in blood bound to carrier proteins.

Only a very remains in a free form in the circulation and has a serum t1/2 of about 5 hours small proportion of vitamin D

So..Exposure to Sun and Then, Fortified Foods….Give Us the D We Need

How Does Vitamin D Facilitate Calcium Absorption in the Intestines??

IN THE INTESTINE

It facilitates intestinal absorption of calcium, as well as stimulates absorption of phosphate and magnesium ions. In the absence of vitamin D, dietary calcium is not absorbed at all efficiently.

Vitamin D stimulates the expression of a number of proteins involved in transporting calcium from the lumen of the intestine, across the epithelial cells and into blood.

The vitamin D form, 1,25-

dihydroxcholecalciferol [1,25(OH)2D3],

1. stimulates the synthesis of the epithelial

calcium channels in the plasma membrane calcium pumps , and

2. induces the formation of the calbindins.

Structure and Synthesis-Vitamin D

The term vitamin D actually refers to a group of steroid molecules. Vitamin D3, also known as cholecalciferol is generated in the skin of animals when light energy is absorbed by a

precursor molecule 7-dehydrocholesterol.

Structure and Synthesis-Vitamin D

Vitamin D is thus not a true vitamin, because individuals with adequate exposure to sunlight do not require dietary supplementation.

There are dietary sources of vitamin D, including egg yolk, fish oil and a number of plants.

The plant form of vitamin D is called vitamin D2 or ergosterol. However, natural diets typically do not contain adequate quantities of vitamin D, and exposure to sunlight or consumption of foodstuffs purposefully supplemented with vitamin D are necessary to prevent deficiencies.

Vitamin D, as either D3 or D2, does not have significant biological activity.

Rather, it must be metabolized within the body to the hormonally-active form.

This transformation occurs in 2 steps, as depicted in the diagram on the next slide

Within the liver, cholecalciferal is hydroxylated to 25-hydroxycholecalciferol by the enzyme 25-

hydroxylase.

Within the kidney, 25-vitamin D serves as a substrate for 1-alpha-hydroxylase, yielding 1,25-dihydroxycholecalciferol, the biologically active form of vitamin D.

Physiological Effects of Vitamin D

Vitamin D is well known as a hormone involved in mineral metabolism and bone growth.

Its most dramatic effect is to facilitate intestinal absorption of calcium, although it also stimulates absorption of phosphate and magnesium ions.


In the absence of vitamin D, dietary calcium is not absorbed at all efficiently.

Vitamin D stimulates the expression of a number of proteins involved in transporting calcium from the lumen of the intestine, across the epithelial cells and into blood. The best-studied of these calcium transporters is calbindin, an intracellular protein that ferries calcium across the intestinal epithelial cell.


Vitamin D receptors are present in most if not all cells in the body. Additionally, experiments using cultured cells have demonstrated that vitamin D has potent effects on the growth and differentiation of many types of cells.

Hence, vitamin D has physiologic effects much broader that a role in mineral homeostasis & bone function.

Diseases and Conditions that Vitamin D Helps Prevent

• Rickets and other bone diseases

• Internal cancers

• Multiple sclerosis

• Helps in pregnacy to make bone stronger

Vitamin D3

Must be Vitamin D3, also known as cholecalciferol.

Dose is 75 IU per pound body weight or 165 IU per kilogram body weight.

Children with blood levels of 25-hydroxy exceeding 80 ng/mL have shown the most improvement in immune response.

Very important in immune function.

Outline

• Historical science perspective

• Diseases and conditions affected by vitamin D

• Sources of vitamin D

• How much we need in our blood

• Concerns regarding ultraviolet radiation

• Sources of additional information

Any Question

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